Université Grenoble Alpes, F-38000, Grenoble, France.
CNRS, ERL5261, F-38000, Grenoble, France.
Sci Rep. 2017 May 18;7(1):2120. doi: 10.1038/s41598-017-02349-0.
Exolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of Pseudomonas aeruginosa strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an exlA-negative strain induced similar tissue injuries. In addition, ExlA conferred on bacteria the capacity to proliferate in lungs and to disseminate in secondary organs, similar to bacteria possessing a functional T3SS. CLJ1 did not promote a strong neutrophil infiltration in the alveoli, owing to the weak pro-inflammatory cytokine reaction engendered by the strain. However, CLJ1 was rapidly eliminated from the blood in a bacteremia model, suggesting that it can be promptly phagocytosed by immune cells. Together, our study ascribes to ExlA-secreting bacteria the capacity to proliferate in the lung and to damage pulmonary tissues, thereby promoting metastatic infections, in absence of substantial immune response exacerbation.
胞外溶素（ExlA）是一种最近被鉴定出的由全球范围内的某些铜绿假单胞菌菌株分泌的一种孔形成毒素，这些菌株缺乏 III 型分泌系统（T3SS），而 T3SS 是一种主要的毒力因子。在这里，我们在超微结构水平上研究了分泌 ExlA 的菌株 CLJ1 在感染小鼠肺部时引起的损伤。CLJ1 诱导了肺细胞和内皮细胞的坏死性损伤，导致肺泡-血管屏障的破坏。在一个 exlA 阴性菌株中异位表达 ExlA 也会诱导类似的组织损伤。此外，ExlA 赋予细菌在肺部增殖和在次级器官中传播的能力，这与具有功能性 T3SS 的细菌相似。CLJ1 并没有在肺泡中引起强烈的中性粒细胞浸润，这是由于该菌株引发的弱促炎细胞因子反应。然而，在菌血症模型中，CLJ1 很快从血液中被清除，这表明它可以被免疫细胞迅速吞噬。总的来说，我们的研究表明，分泌 ExlA 的细菌具有在肺部增殖和损伤肺组织的能力，从而促进转移性感染，而不会引起实质性的免疫反应加重。
